Topical Antifungal Drugs

Topical antifungal drugs treat superficial infections of skin, nails and mucosa caused by dermatophytes, Candida and Malassezia. They are effective for most tinea corporis, cruris, pedis and pityriasis versicolor, but not for tinea capitis or most nail disease, which need oral therapy.

Mechanism. Azoles (clotrimazole, miconazole, econazole, ketoconazole, sertaconazole, luliconazole) inhibit lanosterol 14-alpha-demethylase and ergosterol synthesis. Allylamines (terbinafine, naftifine) inhibit squalene epoxidase, giving fungicidal activity against dermatophytes. Amorolfine inhibits two later sterol enzymes. Ciclopirox chelates metal cations. Nystatin binds membrane ergosterol and is active only against yeasts.

Pharmacokinetics. Low systemic absorption through intact skin. Terbinafine and azoles persist in the stratum corneum after short courses. Nail lacquers penetrate the nail plate slowly.

• Terbinafine 1 percent: most fungicidal for dermatophytes; shortest courses.
• Azoles (clotrimazole 1 percent, miconazole 2 percent, econazole 1 percent, ketoconazole 2 percent): broad activity against dermatophytes, Candida and Malassezia; ketoconazole shampoo for seborrhoeic dermatitis and pityriasis versicolor.
• Amorolfine 5 percent and ciclopirox 8 percent lacquers: for mild nail infection.
• Nystatin: yeast infections only.
• Others: selenium sulphide 2.5 percent (pityriasis versicolor), Whitfield ointment (benzoic and salicylic acid), tolnaftate.

Regimens.

• Tinea corporis and cruris: terbinafine 1 percent once daily for 1 week, or an azole twice daily for 2 to 4 weeks; continue for 1 to 2 weeks after clearance for azoles. Tinea pedis: terbinafine once daily for 1 week (interdigital) or 2 to 4 weeks (moccasin type needs oral therapy).
• Cutaneous candidiasis and intertrigo: clotrimazole or miconazole twice daily for 2 to 4 weeks; nystatin for yeast only; keep skin dry.
• Pityriasis versicolor: ketoconazole 2 percent shampoo once daily for 3 days, or selenium sulphide 2.5 percent for 10 minutes daily for 7 days, or terbinafine solution once daily for 1 week; recurrence is common and prophylaxis with monthly shampoo helps.
• Seborrhoeic dermatitis: ketoconazole 2 percent shampoo or cream twice weekly for 2 to 4 weeks, then once weekly or fortnightly.
• Superficial nail infection (distal, under half of the nail, no matrix involvement): amorolfine 5 percent lacquer once or twice weekly for 6 months (fingernails) to 9 to 12 months (toenails).
• Children: the same agents for short courses.

Selection. Confirm the diagnosis with microscopy (KOH) or culture where available. Avoid combined steroid-antifungal creams except for short courses on inflamed skin. Tinea capitis, extensive disease, nail disease and failure of topical therapy need oral treatment.

Contraindications. Hypersensitivity; nystatin is not used for dermatophytes.

Effects. Burning, itching, erythema, contact dermatitis; rarely systemic effects. Steroid-antifungal mixtures cause atrophy and tinea incognito.

Interactions. Negligible for topical use.

Monitoring. Reassess at 2 to 4 weeks (1 week for terbinafine); if no response, review diagnosis, adherence, and the need for oral therapy.

Special groups. Pregnancy: clotrimazole and miconazole are acceptable; terbinafine topical has low absorption. Breastfeeding: acceptable. Region: tinea capitis in schoolchildren, tinea corporis and extensive tinea from misuse of potent steroid creams are common in East Africa; non-prescription sale of steroid-antifungal combinations contributes to relapsing, atypical disease.